In the present study, PKD1 and PKD2 genes were analyzed in a large Chinese family with ADPKD using denaturing high-performance liquid chromatography and DNA sequencing.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder and is due to disease-causing variants in PKD1 or PKD2.
Autosomal dominant polycystic kidney disease (ADPKD) is a very common inherited disease caused by mutations in PKD1 or PKD2 genes characterized by progressive enlargement of fluid-filled cysts and loss of renal function [1].
Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited cause of renal failure in adults, and is due to loss-of-function mutations in either the PKD1 or PKD2 genes, which encode polycystin-1 and polycystin-2, respectively.
The identification of groups of mutations in the PKD2 gene, which differ significantly with respect to clinical outcome, is to our knowledge the first description of a genotype/phenotype correlation in autosomal dominant polycystic kidney disease.
Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 and is characterized by proliferation of renal tubular epithelium and progressive chronic kidney disease.
While a disease-causing mutation in the PKD1 and PKD2 genes cannot be identified, DNA microsatellite analysis provided an early diagnosis and may be considered in ADPKD families.
Patients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys.
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people.
Moreover, Pkd2(-/-) mice with homozygous PKD2(tg)-transgene alleles (Pkd2(-/-);PKD2(tg/tg)) showed significant further amelioration of the cystic severity compared to that in Pkd2(-/-) mice with a hemizygous PKD2(tg) allele (Pkd2(-/-);PKD2(tg)), suggesting that the ADPKD phenotype was improved by increased transgene dosage.
ADPKD is caused by mutation in one of two genes-85% of cases are caused by mutation in PKD1 on chromosome 16 and 15% of cases are caused by mutation in PKD2 on chromosome 4.
We show that confluent primary ADPKD cyst cells with the novel PC1 mutation DeltaL2433 and with normal abundance of PC1 and PC2 polypeptides lack ciliary PC1 and often lack ciliary PC2, whereas PC1 and PC2 are both present in cilia of confluent normal human kidney (NK) epithelial cells in primary culture.
Therefore, the model Pkd2(WS25/-), which carries the WS25 unstable allele and a true null allele, produces somatic second hits during mouse development or adult life and establishes an extremely faithful model of human ADPKD.